Breast Cancer Risk Independent of Ovarian Stimulation Drugs for Most Patients

Analysis of breast cancer risk for women undergoing fertility treatment is “generally reassuring”

medwireNews: Ovarian stimulation during fertility treatment is not associated with an increased risk of breast cancer for most women, US research suggests.

A median of 30 years of follow-up of 12,193 women treated for infertility between 1965 and 1988 found that the 38.1% of patients who had ever used clomiphene citrate did not have a significantly increased risk of breast cancer compared with patients who had never used the drug, after adjusting for confounders such as gravidity.

And the 9.6% of women treated with gonadotrophins had no significant increased risk of breast cancer regardless of dose, number of cycles and age at the start of treatment, although an increased risk of invasive disease was found for users who were nulligravid at follow-up (hazard ratio [HR]=1.98).

The results for treatment with clomiphene citrate and gonadotrophins are therefore “generally reassuring”, say Louise Brinton, from the National Cancer Institute in Rockville, Maryland, and co-authors in Cancer, Epidemiology, Biomarkers & Prevention.

However, the likelihood of breast cancer rose with the number of clomiphene cycles and with accumulating dose, with a significant increase in risk found for the 96 women who had received six or more cycles, with a cumulative dose of at least 2251 mg (HR=1.27).

Women who began clomiphene treatment after the age of 35 years were also at significantly increased risk of breast cancer compared with nonusers, with a HR of 1.31.

Analysis of data for 696 women diagnosed with breast cancer during follow-up who had validated diagnostic information available revealed an increased risk of any breast cancer (HR=1.45) and invasive disease (HR=1.69) for those who had received 12 or more clomiphene cycles.

But no significant increase was found for in situ breast cancer in women given a high number of repeat clomiphene cycles, “providing little support for the notion of closer surveillance of treated women-as has been suggested for the association of fertility drugs with borderline ovarian cancers”, Louise Brinton et al comment.

While recognising that the risk of invasive breast cancer was found only for clomiphene treatment that “far exceeded” current dosing recommendations, the team cautions that continued monitoring of long-term effects seems warranted, “especially given that our study participants were still relatively young (and had not yet reached their peak incidence for breast cancer) and that ovulation-stimulating drugs, including gonadotropins-potent ovulation stimulators-are increasingly being used in infertility treatment protocols.”


Brinton L, Scoccia B, Moghissi K, et al. Long-term Relationship of Ovulation-Stimulating Drugs to Breast Cancer Risk. Cancer Epidemiol Biomarkers Prev 2014; 23; 584–93. doi: 10.1158/1055-9965.EPI-13-0996

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